Biofunctional hydrogels for skeletal muscle constructs
Salimath, Apoorva Sangam
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Skeletal muscle tissue damage costs the US government hundreds of billions of dollars annually. Meanwhile, there is great potential to use skeletal muscle as a scalable actuator system, covering wide length scales, frequencies, and force regimes. Hence, the interest in soft robotics and regenerative medicine methods to engineer skeletal muscle has increased in recent years. The challenges to generate a functional muscle strip are typical to those of tissue engineering, where common issues such as cell source, material scaffold, bioreactor method or configuration play key roles. Specifically, it is important to translate the existing body of myogenesis knowledge into engineering muscle constructs by examining the impact of the cell microenvironment on growth, alignment, fusion, and differentiation of skeletal muscle cells. The main motivation behind this thesis was to generate a contractile 3D skeletal muscle construct utilizing organized biochemical and physical cues to guide muscle cell differentiation and maturation. Such a construct is expected to play an important role in medical applications and the development of soft robotics. To do this, 3D, swollen hydrogels were chosen to provide tailorable platforms that support cellular activities to similar extents as native matrices. For this work, we utilized an engineered bio-functionalized poly(ethylene glycol)-(PEG)-hydrogel with maleimide (MAL) cross-linking reaction chemistry that gels rapidly with high reaction efficiency under cytocompatible reaction conditions. PEG alone has been shown to have low protein adsorption, a minimal inflammatory profile, well established chemistry, and a long history of safety in vivo. The PEG-MAL system in particular allows “plug-and-play” design variation, control over polymerization time, and small degradation products. To develop an effective soft biomaterial for the development of an aligned, functional muscle construct, we (i) screened hydrogel properties for differentiation, (ii) recreated alignment of skeletal muscle cells, (iii) determined effective generated force upon action of an external agonist. The impact of this study in generating a controllable force actuator will be significant in the construction of biological machines. Concomitantly, this study will provide a unique regenerative solution for skeletal muscle tissue repair and regeneration.